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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 December 2005 - 12 January 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study is performed according to internationally accepted guidelines and under GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Principles of method if other than guideline:
- It is not mentioned in the report if food was withheld overnight before dosing.
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Sponsor's identification: DIFORMAL
Container: glass flask (n= 1)
Quantity: 141.16 g (container + contents)
Batch No: AV 549/2
Active compound: bis-(2-chlorethyl)-formal
Purity: 88.7%
Date received: 09 December 2005
Form: liquid
Colour: colorless
Storage: room temperature
Expiry date: 28.05.2006
It was identified under the code number: PH-05/0398.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage JANVIER (53940 Le Genest St Isle - France)
- Age at study initiation: no data
- Weight at study initiation: 205-234g
- Fasting period before study: no data
- Housing: no data
- Diet (e.g. ad libitum): maintenance diet
- Water (e.g. ad libitum): no data
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 27-48
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data


IN-LIFE DATES: 21 December 2005 - 12 January 2006

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: high dose undilted and other doses diluted in olive oil
Details on oral exposure:
VEHICLE: no data

MAXIMUM DOSE VOLUME APPLIED: 1.63 ml/kg bw

DOSAGE PREPARATION (if unusual): no data

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no data
Doses:
2000, 300, 50 mg/kg bw
No. of animals per sex per dose:
3 female rats in the 2000 and 300 mg/kg bw test groups and 6 female rats in the 50 mg/kg bw test group and the control group.
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed 30 minutes, 1 hour, 3 hours, 4 hours, 24 hours after dosing. Surviving animals were observed daily. Animals were weighed on day 0, 2, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: none
Statistics:
None

Results and discussion

Preliminary study:
Not performed
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 50 - < 300 mg/kg bw
Mortality:
It was noted the death of the 3 treated rats at 2000 mg/kg body weight, 4 hours and 50 minutes following the test item administration.
It was noted the death of the 3 treated rats at 300 mg/kg body weight, 24 hours after the test item administration.
It was noted the death of the 1 treated rat at 50 mg/kg body weight, 48 hours after the test item administration.
Clinical signs:
It was registered for the animals treated at 2000 mg/kg, 1 hour after the test item administration, a decrease of the spontaneous activity (3/3), a decrease of the reflexes (3/3), partially closed eyes (3/3), a decrease of muscle tone (3/3) and a bradypnea. These signs were registered until the death of the animals. It was registered in the treated group at 300 mg/kg, a decrease of the spontaneous activity and a decrease ofthe muscle tone (3/3), 3 and 4 hours after the test item administration. No clinical signs related to the administration ofthe test item at 50 mg/kg were observed.
Body weight:
The body weight evolution of the animals treated at 50 mg/kg remained normal throughout the study, similar between treated and control animals.
Gross pathology:
The macroscopical examination of the animals which died during the study revealed a thickening and redness coloration on the proventricular stomacal mucous. The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The LD50 cut-off of the test item DIFORMAL is 200 mg/kg body weight by oral route in the rat. The LD50 is between 50-300 mg/kg bw and therefore the test substance is placed in Cat III according to GHS.
Executive summary:

The test item DIFORMAL was administered in a first step to a group of 3 females Sprague Dawley rats at the single dose of 2000 mg/kg body weight, in a second step to a group of 3 females Sprague Dawley rats at the single dose of 300 mg/kg body weight and a third step to a group of 6 females Sprague Dawley rats at the single dose of 50 mg/kg body weight according to the experimental protocol established on the basis of the official method as defined in the OECD guideline 423 dated December 11h, 2001 and the test method B.1 tris of the Directive 2004/73/EC. It was noted the death of the 3 treated rats at 2000 mg/kg body weight, 4 hours and 50 minutes following the test item administration. It was noted the death of the 3 treated rats at 300 mg/kg body weight, 24 hours after the test item administration. It was noted the death of the 1 treated rat at 50 mg/kg body weight, 48 hours after the test item administration. It was registered for the animals treated at 2000 mg/kg, 1 hour after the test item administration, a decrease of the spontaneous activity (3/3), a decrease of the reflexes (3/3), partially closed eyes (3/3), a decrease of muscle tone (3/3) and a bradypnea. These signs were registered until the death of the animals. It was registered in the treated group at 300 mg/kg, a decrease of the spontaneous activity and a decrease ofthe muscle tone (3/3), 3 and 4 hours after the test item administration. No clinical signs related to the administration ofthe test item at 50 mg/kg were observed. The body weight evolution of the animals treated at 50 mg/kg remained normal throughout the study, similar between treated and control animals. The macroscopical examination of the animals which died during the study revealed a thickening and redness coloration on the proventricular stomacal mucous. The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes. The LD50 cut-off of the test item DIFORMAL is 200 mg/kg body weight by oral route in the rat. The LD50 is between 50-300 mg/kg bw and therefore the test substance is placed in Cat III according to GHS.